Hereditary early-onset Parkinson's disease caused by mutations in PINK1

Eriza Maria Valente, Patrick M. Abou-Sleiman, Viviana Caputo, Miratul M K Muqit, Kirsten Harvey, Suzana Gispert, Zeeshan Ali, Domenico Del Turco, Anna Rita Bentivoglio, Daniel G. Healy, Alberto Albanese, Robert Nussbaum, Rafael González-Maldonado, Thomas Deller, Sergio Salvi, Pietro Cortelli, William P. Gilks, David S. Latchman, Roberk J. Harvey, Bruno DallapiccolaGeorg Auburger, Nicholas W. Wood

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6. families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.

Original languageEnglish
Pages (from-to)1158-1160
Number of pages3
JournalScience
Volume304
Issue number5674
DOIs
Publication statusPublished - May 21 2004

ASJC Scopus subject areas

  • General

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